The role of cumulative growth hormone exposure in determining mortality and morbidity in acromegaly: a single centre study

Varadhan, Lakshminarayanan; Reulen, Raoul C.; Brown, M.; Clayton, Richard N.

doi:10.1007/s11102-015-0700-3

Cited by 37 publications

(27 citation statements)

References 32 publications

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“…Secondly, low BCAAs levels could act as protective factor for coronary ischemic disease [63,64]. In this regard, it should be noted that, although cardiovascular disease is the principal cause of premature mortality in patients with ACRO, this is not mainly due to ischemic heart attack [4][5][6][7]. In fact, patients with ACRO present a low incidence of heart ischemic disease despite increased cardiovascular risk factors such as diabetes and hypertension [14,[65][66][67][68].…”

Section: Discussionmentioning

confidence: 99%

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Metabolic fingerprint of acromegaly and its potential usefulness in clinical practice

Biagetti¹,

Herance²,

Ferrer³

et al. 2019

EJEA

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Insulin-like growth factor-1 (IGF-1) and growth hormone (GH) levels are the main targets for monitoring acromegaly activity, but they are not in close relationship with the clinical course of the disease and the associated comorbidities. The present study was aimed at identifying metabolites that could be used as biomarkers for a better disease phenotyping. For this purpose, metabolic fingerprint using an untargeted metabolomic approach was examined in serum from 30 patients with acromegaly and 30 age-matched controls. Patients with acromegaly presented fewer branched-chain amino acids (BCAAs) compared to the control group (valine: 4.75 ± 0.87 vs. 5.20 ± 1.06 arbitrary units (AUs), p < 0.05; isoleucine: 2.54 ± 0.41 vs. 2.80 ± 0.51 AUs; p < 0.05). BCAAs were also lower in patients with active disease compared to patients with normal levels of IGF-1 with or without medical treatment. GH, but not IGF-1, serum levels were inversely correlated with both valine and isoleucine. These findings indicate that low levels of BCAAs represent the main metabolic fingerprint of acromegaly and that GH, rather than IGF-1, might be the primary mediator. In addition, our results suggest that the assessment of BCAAs could help to identify active disease and to monitor the response to therapeutic strategies.

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Section: Discussionmentioning

confidence: 99%

“…Although improvements in surgery and medical therapy decreased the mortality in patients with ACRO, it still remains higher than in the general population [4]. This increase in mortality is mainly due to the higher rate of cardiovascular and malignant diseases in comparison with the age-matched general population [4][5][6][7].…”

Section: Introductionmentioning

confidence: 98%

Metabolic fingerprint of acromegaly and its potential usefulness in clinical practice

Biagetti¹,

Herance²,

Ferrer³

et al. 2019

EJEA

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“…Chronic exposure to elevated GH and IGF-I levels in patients with acromegaly is associated with considerable comorbidities such as metabolic dysfunction leading to an increased risk of diabetes mellitus and, if left untreated, increased mortality related to cardiovascular, cerebrovascular, and pulmonary dysfunction (2,3). The aims of treatment are to normalize GH and IGF-I (current guidelines recommend GH <1 µg/L and agenormalized serum IGF-I levels) (4) to ameliorate the signs and symptoms of the disease, as well as to reduce mortality (5,6). Early and successful treatment to control acromegaly could reduce exposure to GH and IGF-I, thereby improving clinical outcomes (2,4,7).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of the Efficacy and Safety of Switching to Pasireotide in Patients With Acromegaly Inadequately Controlled With First-Generation Somatostatin Analogs

et al. 2020

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Introduction: Acromegaly is a rare, serious endocrine disorder characterized by excess growth hormone (GH) secretion by a pituitary adenoma and overproduction of insulin-like growth factor I (IGF-I). Transsphenoidal surgery is the treatment of choice, although many patients require additional interventions. First-generation somatostatin analogs (SSAs) are the current standard of medical therapy; however, not all patients achieve control of GH and IGF-I. Outcomes from a Phase IIIb open-label study of patients with uncontrolled acromegaly on first-generation SSAs switching to pasireotide are reported.Methods: Adults with uncontrolled acromegaly (mean GH [mGH] ≥1 µg/L from a fivepoint profile over 2 h, and IGF-I >1.3× upper limit of normal [ULN]) despite ≥3 months' treatment with maximal approved doses of long-acting octreotide/lanreotide received open-label long-acting pasireotide 40 mg/28 days. Pasireotide dose could be increased (maximum: 60 mg/28 days) after week 12 if biochemical control was not achieved, or decreased (minimum: 10 mg/28 days) for tolerability. Patients who completed 36 weeks' treatment could continue receiving pasireotide during an extension (weeks 36-72) when concomitant medication for acromegaly was permitted. Primary endpoint was proportion of patients with mGH <1 µg/L and IGF-I 2.5 µg/L. Gadelha et al. Pasireotide for Uncontrolled Acromegaly PatientsFor patients who entered the extension, 14.8% (95% CI: 8.1-23.9), 12.5% (95% CI: 6.4-21.3), 14.8% (95% CI: 8.1-23.9) and 11.4% (95% CI: 5.6-19.9) had mGH <1 µg/L and IGF-I

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“…Acromegaly is a systemic disorder characterized by elevated and non-suppressible growth hormone (GH) and increased insulin-like growth factor-1 (IGF-1) levels, almost always caused by GH hypersecretion from a pituitary somatotroph adenoma [1]. Acromegaly has been associated with high mortality and morbidity, particularly when untreated or inadequately controlled [2][3][4][5], and its management includes surgery, medical therapy and radiotherapy. The therapeutic goals are the normalization of IGF-1 and lowering of mean serum GH below a threshold level, the control of tumor growth with preservation of normal pituitary function, along with the relief of symptoms and a decrease in associated comorbidities and/or mortality [6][7][8].…”

Section: Introductionmentioning

confidence: 99%

“…We describe here a patient where immunoreceptor profiling of somatostatin receptor type (SSTR) 2, SSTR5 [13,14,17] and cadherin E [18][19][20] were found to be useful to guide towards a more personalized therapeutic plan [3,13].…”

Section: Introductionmentioning

confidence: 99%

Role of Receptor Profiling for Personalized Therapy in a Patient with a Growth Hormone-Secreting Macroadenoma Resistant to First-Generation Somatostatin Analogues

Alexandraki

Papadimitriou

Mavroeidi

et al. 2019

JPM

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Background: Acromegaly is almost always caused by a pituitary adenoma and is associated with high morbidity and mortality when uncontrolled. Trans-sphenoidal removal of the adenoma is the mainstay of therapy, but fails to control the disease in a significant number of patients who require further treatment. Somatostatin analogues (SSAs) as monotherapy or in combination with growth hormone (GH)-receptor antagonists and/or dopamine agonists are used either alone or in combination following surgical failure to achieve disease control. The use of specific biomarkers may help to individualize the therapeutic plan after surgical failure and direct towards a more personalized approach. Methods: We report a 41-year-old man with acromegaly and residual disease after repeated surgery that was resistant to first-generation SSAs. Results: Biochemical and tumor control were achieved following the administration of a second-generation SSA, pasireotide, combined with pegvisomant, both at maximal doses and along with cabergoline. Histology specimens showed a sparsely-granulated GH-immunostaining pituitary adenoma with intense positivity for somatostatin receptors 2 and 5 and low levels of E-cadherin. Conclusion: Personalized medical therapy guided by currently available biomarkers, such as immunohistochemically-characterized receptor profiling or adhesion molecules, resulted in controlled insulin-like growth factor-1 (IGF-1) and GH levels and symptom alleviation following the combination of three drug-classes.

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The role of cumulative growth hormone exposure in determining mortality and morbidity in acromegaly: a single centre study

Abstract: There has been significant improvement in mortality and morbidity associated with acromegaly, in the setting of routine care in a specialized endocrine unit. Early and effective treatment to 'control' acromegaly could reduce GH exposure and hence vascular comorbidities.

Cited by 37 publications

References 32 publications

Metabolic fingerprint of acromegaly and its potential usefulness in clinical practice

Metabolic fingerprint of acromegaly and its potential usefulness in clinical practice

Evaluation of the Efficacy and Safety of Switching to Pasireotide in Patients With Acromegaly Inadequately Controlled With First-Generation Somatostatin Analogs

Role of Receptor Profiling for Personalized Therapy in a Patient with a Growth Hormone-Secreting Macroadenoma Resistant to First-Generation Somatostatin Analogues

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